With this new function, Mitofusin 2 becomes a viable target to intervene in diseases such as neurodegeneration and cancer.
In the image, the ER of a cell with the Mfn2 protein (left) and without it. On the right, the ER form vesicles which indicates that the organelle is completely disorganized and unable to respond correctly to cellular stress (JP Muñoz)
Each cell in an organism has a sensor that measures the health of its "internal" environment. This "alarm" is found in the endoplasmic reticulum (ER), which is able to sense cellular stress and trigger either rescue responses or the death of the cell. A team from the Institute for Research in Biomedicine (IRB), in Barcelona, has discovered that the protein Mitofusin 2 (Mfn2) plays a crucial role in correctly measuring stress levels, and also makes sure the pathways of cell repair or cell death are effective.
The researchers reveal some of the molecular mechanisms that connect Mfn2 to endoplasmic reticulum stress in the latest edition of the scientific journal, EMBO Journal, from the Nature Group, published by the European Molecular Biology Organization.
When the scientists removed Mfn2 from the cell under conditions of cell stress, the endoplasmic reticulum responded by over-activating the repair pathways. By doing so, it contradictorily functioned worse, reducing the capacity of cells to overcome the stress insult and promoting to a lesser degree apoptotic cell death. “When Mfn2 is removed, the cellular stress response pathways are completely disrupted,” says Antonio Zorzano, coordinator of IRB’s Molecular Medicine Programme and leader of the group “Heterogenic and polygenic diseases".
Not only diabetes
Mfn2 is a mitochondrial protein whose deficiency is related to diabetes. In an earlier publication in Proceedings of the National Academy of Sciences (PNAS), Dr. Zorzano’s research team demonstrated that without Mfn2, tissues become resistant to insulin, a characteristic of diabetes and the so-called metabolic syndrome. In this study, they also observed that the cells had higher endoplasmic reticulum stress.
The current study investigates the relationship between mitochondria and the endoplasmic reticulum, and indicates that changes in mitochondria, caused by the loss of the Mfn2 protein, directly affect the endoplasmic reticulum function. “We have shown that Mfn2 is important for cell viability and has implications for numerous diseases, such as neurodegeration, cancer, cardiovascular disease, in addition to diabetes,” says postdoctoral researcher Juan Pablo Muñoz, first author of the study.
Is Mitofusin 2 a good therapeutic target?
“The fact that we can modulate cell damage response with Mfn2 opens a wide window of possible therapeutic avenues for further study,” says Muñoz. The Chilean scientist at IRB explains that tumour cells don’t activate cell death properly and proliferate uncontrolled. “Cancer cells have already been noted to have low Mfn2 levels, and if we could increase such levels, we would be able to promote apoptosis,” he continues. According to this, other research teams have already published work indicating that the overexpression of Mfn2 induce apoptosis.
To demonstrate the utility of Mfn2 as a target, the researchers now need to find a small molecule, or drug, that modulates its expression in animals. “Our work published on Mfn2 is a proof of concept that highlights the importance of this mitochondrial protein for cell health,” says Zorzano. One of the challenges of the group is to secure funding to perform a massive screening of molecules with the ability to modulate Mfn2 expression and confirm its effects in mice.Reference article:
The EMBO Journal (2013) 32, 2348 - 2361. doi:10.1038/emboj.2013.168
Sònia Armengou | EurekAlert!
New Model of T Cell Activation
27.05.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau
Fungi – a promising source of chemical diversity
27.05.2016 | Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie - Hans-Knöll-Institut (HKI)
A biological and energy-efficient process, developed and patented by the University of Innsbruck, converts nitrogen compounds in wastewater treatment facilities into harmless atmospheric nitrogen gas. This innovative technology is now being refined and marketed jointly with the United States’ DC Water and Sewer Authority (DC Water). The largest DEMON®-system in a wastewater treatment plant is currently being built in Washington, DC.
The DEMON®-system was developed and patented by the University of Innsbruck 11 years ago. Today this successful technology has been implemented in about 70...
Permanent magnets are very important for technologies of the future like electromobility and renewable energy, and rare earth elements (REE) are necessary for their manufacture. The Fraunhofer Institute for Mechanics of Materials IWM in Freiburg, Germany, has now succeeded in identifying promising approaches and materials for new permanent magnets through use of an in-house simulation process based on high-throughput screening (HTS). The team was able to improve magnetic properties this way and at the same time replaced REE with elements that are less expensive and readily available. The results were published in the online technical journal “Scientific Reports”.
The starting point for IWM researchers Wolfgang Körner, Georg Krugel, and Christian Elsässer was a neodymium-iron-nitrogen compound based on a type of...
In the Beyond EUV project, the Fraunhofer Institutes for Laser Technology ILT in Aachen and for Applied Optics and Precision Engineering IOF in Jena are developing key technologies for the manufacture of a new generation of microchips using EUV radiation at a wavelength of 6.7 nm. The resulting structures are barely thicker than single atoms, and they make it possible to produce extremely integrated circuits for such items as wearables or mind-controlled prosthetic limbs.
In 1965 Gordon Moore formulated the law that came to be named after him, which states that the complexity of integrated circuits doubles every one to two...
Characterization of high-quality material reveals important details relevant to next generation nanoelectronic devices
Quantum mechanics is the field of physics governing the behavior of things on atomic scales, where things work very differently from our everyday world.
When current comes in discrete packages: Viennese scientists unravel the quantum properties of the carbon material graphene
In 2010 the Nobel Prize in physics was awarded for the discovery of the exceptional material graphene, which consists of a single layer of carbon atoms...
24.05.2016 | Event News
20.05.2016 | Event News
19.05.2016 | Event News
27.05.2016 | Awards Funding
27.05.2016 | Life Sciences
27.05.2016 | Life Sciences